The ability of macrophages to destroy foreign cells such as bacteria and neoplastic cells forms the basis of an important mechanism of host defense. Although macrophage cytocidal activity appears to be a composite of three reactions involving activation, recognition and target cell killing, detailed information of the mechanism involved in these processes has remained scarce. This proposal seeks to elucidate the molecular events which lead to macrophage activation and to determine the effect of activation on macrophage recognition reactions and effector sell function. Particular emphasis will be placed on the purification and characterization of the soluble T lymphocyte product, denoted macrophage activating factor (MAF), which is responsible for inducing macrophage cytocidal activity. The unique approach to purification which will be used in these studies is the use of an existing T cell hybridoma which has been found to produce MAF and the use of a sensitive and quantitative assay for MAF. Using partially puirified or purified MAF presentations, the mechanism of action of this lymphokine will be determined. Because of the recent reports that certain complement proteins can mimic specific lymphokines and influence activation mononuclear phagocytes, the role of complement in the induction of macrophage cytocidal activity will also be examined. The membrane structures on macrophages which recognize target cells will be characterized. Phagocyte complement receptors will also be defined. A detailed analysis will be performed to quantitate the effects of activation on the function of these two types of cellular recognition structures. The results of these studies should provide additional insights into the molecular basis of macrophage function and thus enhance our understanding of the host defense system.